How to Cite this Article: Gripp KW, Kuryan R, Schnur RE, Kothawala M, Davey LR, Antunes MJ, Reichard KW, Schneider A, Hall BD. 2011. Grade 1 microtia, wide anterior fontanel and novel type tracheo-esophageal fistula in methimazole embryopathy. Am J Med Genet Part A 155: 526–533.
Grade 1 microtia, wide anterior fontanel and novel type tracheo-esophageal fistula in methimazole embryopathy†
Article first published online: 22 FEB 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 3, pages 526–533, March 2011
How to Cite
Gripp, K. W., Kuryan, R., Schnur, R. E., Kothawala, M., Davey, L. R., Antunes, M. J., Reichard, K. W., Schneider, A. and Hall, B. D. (2011), Grade 1 microtia, wide anterior fontanel and novel type tracheo-esophageal fistula in methimazole embryopathy. Am. J. Med. Genet., 155: 526–533. doi: 10.1002/ajmg.a.33705
- Issue published online: 24 FEB 2011
- Article first published online: 22 FEB 2011
- Manuscript Accepted: 17 AUG 2010
- Manuscript Received: 6 JUL 2010
- cutis aplasia;
- iris coloboma;
- retinal coloboma;
- tracheo-esophageal fistula
Carbimazole (CMZ) and its active metabolite methimazole (MMI) are antithyroid medications, which can result in MMI/CMZ embryopathy in susceptible individuals. The incidence of birth defects related to MMI/CMZ embryopathy remains unclear as several epidemiologic studies failed to prove a correlation, despite positive case–control studies and numerous case reports. Malformations reported in exposed individuals and commonly recognized as MMI/CMZ embryopathy include cutis aplasia of the scalp, choanal atresia, esophageal atresia (EA), tracheo-esophageal fistula (TEF), persistent vitelline duct, athelia/hypothelia, and subtle facial dysmorphisms including sparse or arched eyebrows. Here, we report on individuals with early pregnancy exposure to MMI, with microtia and various other anomalies associated with MMI embryopathy, suggesting that microtia is also seen with increased frequency after prenatal MMI exposure. Additional unusual malformations among our patients include a previously unreported type of TEF with three separate esophageal pouches and a fistula connecting the middle pouch to the trachea in one child, and absence of the gall bladder in another. An enlarged anterior fontanel was seen in three patients, and clinodactyly of the fifth finger was noted in three. The similarities between our three patients with microtia after MMI exposure and the two previously reported with microtia after CMZ exposure support the concept of microtia being related to the MMI/CMZ exposure. Recognition of microtia as a manifestation of MMI/CMZ embryopathy will likely increase the number of diagnosed cases and thus affect ascertainment. We propose diagnostic criteria for MMI/CMZ embryopathy, including the presence of at least one major characteristic finding. © 2011 Wiley-Liss, Inc.